The Justicia genus of the family Acanthaceae is the largest genus in the family Acanthaceae, consists of about 600 species, and is found in pantropical and tropical climate areas. Plants belonging to the Justicia genus are perennial plants or subshrubs and are easily recognized by their lip-shaped corolla. Typical plants belonging to the Justicia genus include Justicia procumbens L., Justicia pectoralis Jacq., Justicia gendarussa Burm. f., Justicia anselliana, and Justicia adhatoda L, etc., but the physiological activities of plants of the Justicia genus have not yet been sufficiently studied.
Justicia procumbens L. belonging to the Justicia genus of the Acanthaceae is an annual plant and is distributed in Korea, Japan, China, India, etc. Justicia procumbens L. has a height of about 30 cm, and its leaves are opposite leaves, long oval in shape, 2-4 cm in length, and 1-2 cm in width. In addition, both ends of the leaf are pointed, and the edges of the leaf are elliptical or have a wave shape. The flower of the plant is light magenta in color, blooms in July to September, and bear fruit in September to October.
In 1963, Gell P. G. H. & Coombs R. R. A largely classified hypersensitivity, which occurs in the human body, into four types: type I hypersensitivity corresponding acute allergic reactions, and type II-IV hypersensitivity corresponding to non-allergic reactions such as autoimmune diseases (Gell P G H & Coombs R R A, et al. Oxford, England: Blackwell, 1963).
Allergy is defined as a phenomenon in which a living body coming in contact with a foreign substance called allergen shows abnormal responses to the substance. Allergy can be caused not only by various allergens, including pollen, drugs, vegetable fibers, bacteria, foods, hair dyes, chemicals, etc., but also by humidity, temperature, exercise, etc, and can cause various diseases such as allergic rhinitis, asthma, atopic dermatitis, allergic conjunctivitis, allergic otitis media, allergic gastroenteritis, anaphylaxis and urticaria.
Allergic reactions are characterized by being dependent mostly on IgE antibody, and allergic reactions that are mediated by this IgE antibody are named “atopy” (Mitsuyasu et al. Ile50Val variant of IL4Rα upregulates IgE synthesis and associates with atopic asthma. Nature genetics 19.2, 119-120, 1998). Th2 lymphocytes activated by allergen secrete various physiologically active substances (cytokines) such as interleukin-4 (IL-4) or interleukin-5 (IL-5), and these physiologically active substances stimulate B lymphocytes to promote IgE antibody secretion (SHIMODA et al. Lack of IL-4-induced Th2 response and IgE class switching in mice with disrupted State6 gene. Nature 380, 630-633, 1996). The secreted IgE antibodies bind to FceR1 on the surface of cells such as mast cells or basophils to activate these cells. It is known that the activated cells are degranulated to promote the secretion of various physiologically active substances including histamine, leukotrien, prostaglandin D2 or the like that cause various allergic disease-related reactions such as vasodilation, smooth muscle contraction, mucous secretion or the like, and various respiratory disease-related reactions such as airway inflammation, airway contraction or the like (Bjorck, T., & Dahlen, S. E. Leukotrienes and histamine mediate IgE-dependent contractions of human bronchi: pharmacological evidence obtained with tissues from asthmatic and non-asthmatic subjects. Pulmonary pharmacology, 6(1), 87-96, 1993; Stone et al., IgE, mast cells, basophils, and eosinophils. Journal of Allergy and Clinical Immunology, 125(2), S73-S80, 2010).
Furthermore, it was reported that allergic reactions can cause eosinophilia in which the number of eosinophils in blood increases and which is associated with allergic rhinitis and asthma, atopic dermatitis, etc. (Mullarkey et al. Allergic and nonallergic rhinitis: their characterization with attention to the meaning of nasal eosinophilia. Journal of Allergy and Clinical Immunology 65.2 122-126, 1980; Humbles et al. Acritical role for eosinophils in allergic airways remodeling. Science 305.5691, 1776-1779, 2004; Grewe et al. A role for Th1 and Th2 cells in the immunopathogenesis of atopic dermatitis. Immunology today 19.8, 359-361, 1998). Particularly, it is known that an increase in the number of eosinophils in lung tissue is a major factor that causes eosinophilic asthma and eosinophilic pneumonia and that interleukin-5 and eotaxin are substances that induce an increase in the number of eosinophils in a particular tissue (Van Oosterhout et al. Effect of anti-IL-5 and IL-5 on airway hyperreactivity and eosinophils in guinea pigs American Review of Respiratory Disease 147.3, 548-552, 1993; Ying et al. Eosinophil chemotactic chemokines (eotaxin, eotaxin-2, RANTES, monocyte chemoattractant protein-3 (MCP-3), and MCP-4), and CC chemokine receptor 3 expression in bronchial biopsies from atopic and nonatopic (Intrinsic) asthmatics. The Journal of Immunology 163.11, 6321-6329, 1999).
Based on the studies as described above, there have been steady efforts to inhibit IgE antibody secretion, inhibit the degranulation of mast cells or basophils, and block the entry of inflammatory cells such as eosinophils, thereby preventing, treating or improving allergic disease.
Allergy-related diseases are classified, according to the body area in which symptoms occurred, into allergic rhinitis, asthma, hypersensitive pneumonitis, eosinophilic pneumonia, atopic dermatitis, contact dermatitis, urticaria, angioedema, anaphylaxis, allergic conjunctivitis, eosinophilic gastroenteritis, oral allergy syndrome, etc. In addition, allergy-related diseases are classified, according to the cause, into occupational asthma, occupational rhinitis, occupational dermatitis, food-induced urticaria, food-dependent anaphylaxis, anaphylaxis occurring after insect bites, skin rash caused by the wearing of rubber gloves, drug-induced urticaria, anaphylaxis occurring after examination with contrast medium vessel, Churg-Strauss syndrome, idiopathic eosinophilia, etc.
As therapeutic agents for treating allergic diseases, antihistamine drugs, antileukotriene drugs, steroidal drugs and the like have been mainly used, but the use thereof is limited because of their effects and side effects.
Specifically, antihistamine drugs, decongestants, antileukotriene drugs and the like have been used to treat allergic rhinitis. However, antihistamine drugs can cause side effects such as sleepiness, and decongestants such as pseudoephedrine are narcotic components that can cause headache or stroke, and antileukotriene drugs can cause neuropsychiatry-related side effects such as depression, suicide impulse or the like.
More specifically, drugs that are used to treat asthma include antileukotriene drugs, steroidal drugs, beta-2 adrenergic agonists, anti-IgE drugs (Omalizumab) and the like. Herein, in the case of antileukotriene drugs, it is mainly used as mild or add-on therapy, because these cause side effects as described above and also have insignificant effects on asthma. Steroidal therapeutic agents are used mainly for inhalation rather than oral administration due to their side effects, and thus shows poor compliance compared to oral drugs. In addition, beta-2 adrenergic agonists are also inhalation drugs that alleviate asthma symptoms by effectively inhibiting bronchoconstriction through local smooth muscle relaxation of the lung, but do not radically cure asthma and may exacerbate asthma upon long-term administration (Salpeter, et al. Meta-analysis: effect of long-acting β-agonists on severe asthma exacerbations and asthma-related deaths. Annals of internal medicine 144.12 904-912, 2006). Anti-IgE drugs (Omalizumab) are used for severe asthma resistant to steroids/beta-2 adrenergic agonists and have excellent effects, but have disadvantages in that they are expensive and are used as injectable formulations that are not easy to administer.
For treatment of atopic dermatitis, steroidal drugs, immunosuppressants/immunomodulators, antihistamine drugs etc., are used. Immunosuppressants such as Tacrolimus have excellent effects, but can cause side effects such as hypertension, reduced renal function or the like.
As described above, it is obvious that agents that are currently used to treat allergy-related diseases are limited in their use, and thus there is an urgent need to develop new therapeutic agents. In addition, because of complex action mechanisms associated with allergy, there is increasing interest in herbal extracts having effects on a combination of various mechanisms through various components, rather than single-component synthetic drugs that mainly control single targets. However, reports on herbal extracts having excellent effects against a combination of various allergic diseases are still insufficient. Accordingly, there is an urgent need to develop new herbal plant extracts that are safe for use in vivo and that can substitute for conventional anti-allergic drugs.